› 5nx1

X-ray diffraction
1.85Å resolution

Combinatorial Engineering of Proteolytically Resistant APPI Variants that Selectively Inhibit Human Kallikrein 6 for Cancer Therapy

Released:
DOI: 10.2210/pdb5nx1/pdb
PDB entry 5nx1 coloured by chain, front view.
PDB entry 5nx1 coloured by chain, side view.
PDB entry 5nx1 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.
Sananes A, Cohen I, Shahar A, Hockla A, De Vita E, Miller AK, Radisky ES, Papo N
J Biol Chem 293 12663-12680 (2018)
PMID: 29934309

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138354 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (4 distinct):
Kallikrein-6 Chain: A
Molecule details ›
Chain: A
Length: 223 amino acids
Theoretical weight: 24.42 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: Q92876 (Residues: 22-244; Coverage: 98%)
Gene names: KLK6, PRSS18, PRSS9
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases
Soluble APP-beta Chain: B
Molecule details ›
Chain: B
Length: 25 amino acids
Theoretical weight: 2.95 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P05067 (Residues: 289-301; Coverage: 2%)
Gene names: A4, AD1, APP
Soluble APP-beta Chain: D
Molecule details ›
Chain: D
Length: 56 amino acids
Theoretical weight: 6.3 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P05067 (Residues: 302-346; Coverage: 6%)
Gene names: A4, AD1, APP
Sequence domains: Kunitz/Bovine pancreatic trypsin inhibitor domain
Structure domains: Pancreatic trypsin inhibitor Kunitz domain
Soluble APP-beta Chain: C
Molecule details ›
Chain: C
Length: 81 amino acids
Theoretical weight: 9.22 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P05067 (Residues: 289-346; Coverage: 8%)
Gene names: A4, AD1, APP
Sequence domains: Kunitz/Bovine pancreatic trypsin inhibitor domain
Structure domains: Pancreatic trypsin inhibitor Kunitz domain

Ligands and Environments

No bound ligands
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID30B
Spacegroup: P212121
Unit cell:
a: 59.543Å b: 77.702Å c: 92.207Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.186 0.184 0.226
Expression systems:
  • Trichoplusia ni
  • Komagataella phaffii GS115

Quick links

Citations

3 review citations

Remodelling of the tumour microenvironment by the kallikrein-related peptidases.
Srinivasan et al. (2022)
2 more

3 mentions without citation

A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.
Sananes et al. (2018)
2 more